Cyclin A/cdk2 regulates adenomatous polyposis coli-dependent mitotic spindle anchoring.

ABSTRACT: Mutations in adenomatous polyposis coli (APC) protein is a major contributor to tumor initiation and progression in several tumor types. These mutations affect APC function in the Wnt-beta-catenin signaling and influence mitotic spindle anchoring to the cell cortex and orientation. Here we report that the mitotic anchoring and orientation function of APC is regulated by cyclin A/cdk2. Knockdown of cyclin A and inhibition of cdk2 resulted in cells arrested in mitosis with activation of the spindle assembly checkpoint. The mitotic spindle was unable to form stable attachments to the cell cortex, and this resulted in the spindles failing to locate to the central position in the cells and undergo dramatic rotation. We have demonstrated that cyclin A/cdk2 specifically associates with APC in lat

SUBMITTER: Beamish H 

PROVIDER: S-EPMC2781448 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature